In a recent publication in the New England Journal of Medicine, researchers from Washington University School of Medicine in St. Louis, Missouri revealed that the risk of developing long-term COVID-19 and its related complications declined significantly over the course of the COVID-19 pandemic due to vaccination, but the risks persist.

For this study, the researchers sought to estimate the cumulative incidence of postacute sequelae of SARS-CoV-2 infection (PASC) 1 year after SARS-CoV-2 infection during the pre-Delta, Delta, and Omicron eras of the COVID-19 pandemic.

The authors wrote, “Postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) can affect many organ systems. However, temporal changes during the coronavirus disease 2019 (COVID-19) pandemic, including the evolution of SARS-CoV-2, may have affected the risk and burden of PASC. Whether the risk and burden of PASC have changed over the course of the pandemic is unclear.”

Between March 1, 2020, and January 31, 2022, researchers gathered and compared data from health records from the Department of Veterans Affairs to generate a study population that included 441,583 veterans with SARS-CoV-2 infection and 4,748,504 noninfected contemporaneous controls.

The researchers divided the veterans into five groups: 1) unvaccinated COVID-19 sufferers who acquired the original strain in 2020; 2) the Delta variant in 2021; and 3) the Omicron variant in 2022. The other two groups included: 4) vaccinated individuals who had the Delta variant, and 5) vaccinated individuals with Omicron. No vaccines existed while the original strain circulated.

The results revealed that among unvaccinated individuals infected with SARS-CoV-2, the cumulative incidence of PASC during the first year after infection was 10.42 events per 100 persons in the pre-Delta era, 9.51 events per 100 persons in the Delta era, and 7.76 events per 100 persons in the Omicron era (difference between the Omicron and pre-Delta eras, –2.66 events per 100 persons; difference between the Omicron and Delta eras, –1.75 events per 100 persons).

Among vaccinated individuals, the cumulative incidence of PASC at 1 year was 5.34 events per 100 persons during the Delta era and 3.50 events per 100 persons during the Omicron era (difference between the Omicron and Delta eras, –1.83 events per 100 persons). Vaccinated individuals had a lower cumulative incidence of PASC at 1 year compared with unvaccinated persons (difference during the Delta era, –4.18 events per 100 persons; difference during the Omicron era, –4.26 events per 100 persons). Decomposition analyses disclosed 5.23 fewer PASC events per 100 persons at 1 year during the Omicron era than during the pre-Delta and Delta eras combined; 28.11% of the decrease was attributable to era-related effects (changes in the virus and other temporal effects), and 71.89% was attributable to vaccines.

“The cumulative incidence of PASC during the first year after SARS-CoV-2 infection decreased over the course of the pandemic, but the risk of PASC remained substantial even among vaccinated persons who had SARS-CoV-2 infection in the omicron era,” the authors concluded.

The researchers indicated that an estimated 70% of the risk reduction was due to vaccination against COVID-19 and 30% to changes over time, including the SARS-CoV-2 virus’s evolving characteristics and enhanced recognition of the virus and its management.

“The research on declining rates of long COVID marks the rare occasion when I have good news to report regarding this virus,” stated the study’s senior author, Ziyad Al-Aly, MD, a Washington University clinical epidemiologist and global leader in COVID-19 research. “The findings also show the positive effects of getting vaccinated.”

Dr. Al-Aly also stressed that even with the overall decline, the lowest rate—3.5%—remains a significant risk. “That’s three to four vaccinated individuals out of 100 getting long COVID,” he said. “Multiplied by the large numbers of people who continue to get infected and reinfected, it’s a lot of people. This remaining risk is not trivial. It will continue to add an already staggering health problem facing people across the world.”

Moreover, Dr. Al-Aly added, “You can see a clear and significant difference in risk during the delta and omicron eras between the vaccinated and unvaccinated. So, if people think COVID is no big deal and decide to forgo vaccinations, they’re essentially doubling their risk of developing long COVID.”

Dr. Al-Aly also indicated that another noteworthy discovery provided vital information regarding the virus’s evolution and stated that while investigating the risk among all individuals infected with COVID-19 during the Omicron era of 2022, the possibility of heart, brain, kidney, and lung problems decreased. In contrast, diseases and illnesses related to metabolic function and the gastrointestinal system expanded.

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